New developments in Alzheimer's treatments

In our current understanding of this disease, it has no cure. However, there are many treatment options available that seek to manage the disease and slow its progression , and new research is being conducted every day to find a cure. Early detection and intervention can also help slow the progression of the disease and improve outcomes.

In this article, we take a look at AD in depth, how it affects the brain and its functioning, the risk factors, treatment options, and explore breakthroughs that are moving closer to finding a cure.

Symptoms and diagnosis

One of the biggest challenges with AD is its early detection, as some of the symptoms are similar to normal signs of aging, making early detection difficult. AD is typically seen in people above the age of 65, although in some cases, the symptoms can manifest earlier. 

The severity of the disease varies from person to person, with some of the common symptoms including memory loss, difficulty in completing familiar tasks, disorientation, communication problems, changes in mood, decreased judgment, and personality changes. 

The disease usually progresses gradually, with some memory loss being one of the earliest symptoms. On average, a person lives 4 to 8 years after being diagnosed with AD. However, some people can live for 20 years or more following diagnosis. 

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There is no single diagnostic test for AD. Instead, doctors use a combination of neurological exams, medical history, brain imaging (including CT, PET, and MRI scans), and blood tests to make a diagnosis. 

Even though much about the onset of the disease is a mystery, the buildup of proteins in the brain has been linked to neural degeneration. This includes buildup of amyloid beta, which forms senile plaques, and phosphorylated tau protein, which forms neurofibrillary tangles. This buildup generally happens in the hippocampus, which is responsible for memory storage, spatial navigation, and learning.

Risk factors

Despite our limited knowledge of the exact cause of AD, genetics is known to play a role in the development of at least some forms of the disease. The mutation of three genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN 2), is known to cause a type of AD termed familial AD; and presence of one form of the polymorphic protein Apolipoprotein E (APOE) is a strong genetic risk factor for a type of AD termed sporadic AD. The mutations cause the production of abnormal proteins which are associated with AD. In addition, individuals with a genetic predisposition to AD are more likely to develop the disease than those without. 

Lifestyle factors such as exercise, sleep, and diet have also been linked to risk. According to the NHS, certain risk factors associated with cardiovascular disease can also increase the risk of AD. These include smoking, obesity, high cholesterol and blood pressure, and diabetes. 

The Alzheimer's Society recommends regular exercise to reduce the risk of AD and dementia. However, according to a study by Leon Flicker from the University of Western Australia, Perth, decisions on whether or not to modify lifestyle factors should depend on the individual. This is because, as human trials are not possible for the study of many modifiable lifestyle factors, decisions regarding their impact on Alzheimer's disease are based primarily on observational data.

However, this hesitancy does not include sleep. Sleep is required for the neural pathways in the brain to function well. Studies have shown that insomnia and sleep deprivation can lead to an accumulation of the amyloid beta protein, as well as the tau protein in the brain.

A study led by Archana Gaur from the All India Institute of Medical Science, Hyderabad, points out that this causes a vicious cycle. People with AD have sleep disturbances, which disrupt their sleep cycle, while the sleep disturbance can induce AD.

Therefore, lack of sleep can be a preventable risk factor for neurodegeneration. However, AD is a complex disease with many possible risk factors and it is not caused by lack of sleep alone.

Treatment and management

Even though AD has no known cure, there are several treatment options which can slow the progression of the disease. The treatment itself varies depending on the severity of the disease, as certain medications only work for early-stage AD. 

Cholinesterase inhibitors have been shown to help to reduce or control behavioral and cognitive symptoms in early-stage AD. Their purpose is to keep acetylcholine, a neurotransmitter thought to be vital for memory, from breaking down.

Some immunotherapies, such as lecanemab and aducanumab, have also been approved by the FDA for the treatment of early-stage AD. These medications work by reducing beta-amyloid plaques in the brain.

There are also a few treatments available for people with moderate to severe AD. Memantine is a partial N-methyl-D-aspartate (NMDAR) receptor antagonist and helps some people perform day-to-day tasks for longer than they would be able to without the medicine. Scientists think it works by controlling the production of glutamate, which in large amounts can lead to brain cell death.

The FDA has also approved donepezil, which can result in a slight improvement in brain function. However, there is no evidence to suggest that donepezil alters the progression of AD. 

Due to the complexity and severity of the disease, the best course of action is early detection, especially for those with a genetic predisposition to the disease. This includes regular checkups and maintaining a healthy lifestyle, with regular exercise and adequate sleep. 

A few studies have also suggested cognitive behavioral therapy as a side-effect-free option for neuropsychiatric symptoms. These can help improve the quality of life for individuals with AD and their caregivers but cannot alter the progression of the disease.

Promising advances

Intriguingly, some promising new studies have the potential to point the way to a cure, or at least much more effective treatment.

A new study published in the Annals of Neurology found that suvorexant, a common insomnia medication, decreased the buildup of amyloid beta and tau proteins in the brain.

Suvorexant is a medication commonly prescribed for the treatment of insomnia. The researchers found that suvorexant decreased the concentrations of the proteins in the central nervous system. They suggest that the FDA-approved medication could be repurposed as a treatment for AD. 

According to Eli Lilly, their drug donanemab slowed down the progression of AD by a third in clinical trials. Their trials showed that donanemab, given monthly, slowed the progression of Alzheimer's by about 29% overall and helped patients' continue more of their daily lives and activities. 

However, brain swelling was seen as a common side effect, and two, and possibly three, patients in the study died as a result of its use. Future studies and trials are required to give us more information about the drug and its efficacy and side effects. 

Another study, by scientists from John Hopkins University, has identified a sugar molecule the researchers call RPTPζ^S3L as a potential contributor to AD. RPTPζ^S3L binds to specific receptors in the brain, thus affecting the brain's capacity to eliminate harmful proteins that contribute to AD.

This research could have significant consequences for the diagnosis and treatment of AD. If RPTPζ^S3L can be used as a diagnostic marker for AD, it would allow doctors to make a much faster diagnosis and therefore provide earlier treatment options.

Further, the discovery of this protein provides a possible target for the development of novel therapies for AD.

Conclusion

Early detection and treatment is the best way to deal with AD, especially in people who have a genetic predisposition.

The new studies and research offer a ray of hope to those going through this experience, as breakthroughs might be just around the corner.